rats (SHR) have been reported to differ from those of normotensive Wistar-Kyoto (WKY) rats in response to drugs. The thoracic aorta of SHR gave a smaller relaxant response to acetylcholine (ACh), adenosine (ADO), and isoproterenol (ISO) than did the aorta of WKY.1 " 3 Other investigators found that the ADO-and ISO-induced relaxant responses of the thoracic aorta, perfused mesenteric artery, and perfused hindlimb of SHR were greater than those of WKY.4 " 6 Finally, the contractile response to norepinephrine (NE) of the SHR aorta was either equal to 7 or smaller than 4 8 that of the WKY aorta, but the response of the SHR hindquarters was greater than the WKY counterparts.5 -9 "" The discrepancies remain unexplained but it now appears that the role of the endothelium needs to be considered.In The present work was undertaken to reassess the possible contribution of endothelium to the responses of rat arteries to ACh, ADO, and ISO and, second, to the differences between arteries of SHR and WKY. In addition to the commonly used thoracic aorta and relaxant responses, the femoral artery and NE-induced contraction were studied for comparison purposes. MethodsMale 15-to 16-week-old age-matched SHR and WKY were used. Mean body weights of these rats were 293 ± 5.5 g (n = 17) and 317 ± 4.3 g (n = 20) respectively. Mean systolic blood pressure of SHR and WKY were 186.1 ± 2.3 mm Hg (n = 17) and 135.4 ± 2.0 mm Hg (n = 20) (p < 0.001) by the tail-cuff method in the unanesthetized state. The rat was anesthetized by intraperitoneal pentobarbital (50 rhg/kg) and exsanguinated. The-thorax was opened, and the descending thoracic aorta and femoral artery were immediately excised. After removal of loose connective tissue, a 3 mm-long cylindrical segment was cut from each artery. An adjacent segment was taken after destruction of endothelium; the intimal surface of the aorta was gently rubbed by a wooden rod 1 mm in diameter and that of the femoral artery by a 24-gauge 881 by guest on May 11, 2018 http://hyper.ahajournals.org/ Downloaded from

When examined by fluorescence microscopy the rabbit basilar artery contains a rich adrenergic-like plexus at the adventitiomedial junction. The fluorescence disappears upon chronic reserpinization and bilateral superior cervical ganglionectomy. Transmural stimulation of intramural nerves a results in a response which is predominantly constrictor but also contains a small, inconstant dilator component. The constrictor response is abolished by chronic reserpinization, bilateral superior cervical ganglionectomy, and cold storage of the preparation. The constriction is prevented by the adrenergic neuron blocking agents guanethidine and bretylium but not by such alpha-adrenergic receptor blocking agents as phenoxybenzamine (PBZ), phentolamine, and tolazoline. Our results show that doses of the three latter agents sufficient to abolish contractions to norepinephrine (NE) in concentrations of up to 10(-2) M only potentiate and prolong the contractile response to nerve stimulation. The beta-adrenergic receptor blocking agent, propranolol, and inhibitors of NE neuronal uptake, such as desipramine (desmethylimipramine, DMI) and cocaine, do not influence the size of the neurogenic response. These results suggest that the vasoconstrictor component of the rabbit basilar artery response to transmural nerve stimulation (TNS) is mediated via sympathetic adrenergic-like neurons, but at the same time also raise the question whether the transmission process is typical of classic adrenergic neuroeffector mechanisms.

The isolated taenia coli of the guinea pig takes up tritiated adenosine, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate, in preference to tritiated inosine and adenine. After uptake, [(3)H]adenosine is converted and retained primarily as [(3)H]adenosine triphosphate. Tritium is released from taenia coli treated with [(3)H]adenosine upon activation of the nonadrenergic inhibitory nerves. These results are consistent with the previous evidence that adenosine triphosphate may be the transmitter from the nerves.

SUMMARY Transmural nerve stimulation (TNS) with 0.3-msec pulses between 1 and 25 Hz dilated cat cerebral artery segments in the presence of active muscle tone. Maximum vasodilatation occurred at 8 Hz. The dilator response to exogenous acetylcholine, but not to TNS, was abolished by atropine. Neither physostigmine nor hemicholinium affected the dilator response to TNS, which persisted after administration of guanethidine, phenoxybenzamine, propranolol, reserpine, and chronic sympathectomy. However, it was abolished by tetrodotoxin and cold storage. When examined histochemically, cat and rabbit cerebral arteries exhibited a rich plexiform distribution of acetylcholinesterase which was not affected appreciably by sympathetic denervation. These results suggest that vasodilation is not mediated through modification of sympathetic activity. They also indicate the existence of a nonadrenergic, possibly noncholinergic, vasodilator innervation in cat cerebral arteries. Preliminary studies suggest that the transmitter is not histamine, ATP, prostaglandins, y-aminobutyric acid, dopamine, or serotonin. The cat cerebral artery segments contrast with the isolated rabbit cerebral arteries which predominantly constrict in response to TNS and show a small dilator response.THERE IS AMPLE evidence that cerebral blood vessels of several species receive both sympathetic and nonsympathetic innervation. Based on anatomical and physiological observations,'" 3 it seems likely that the nonsympathetic neurons are part of the parasympathetic nervous system, that they are dilator nerves, and that they run via the greater superficial petrosal nerve to the cerebral blood vessels. Mchedlishvili and Nikolaishvili 4 have stated that this dilator innervation is important in regulating cerebral blood flow, although no significant changes in this parameter resulted when the petrosal nerve or vagus nerve was stimulated electrically. -6 Subsequent reports by other investigators using morphological techniques support the possibility of innervation of cerebral blood vessels by nonsympathetic nerves. Electron microscopy has revealed two different types of vesicles in the nerve terminals of cerebral blood vessels.7 ' 8 The agranular type of vesicles has been considered nonsympathetic and cholinergic in nature. This was supported by the demonstration of acetylcholinesterase in the cerebral blood vessels. 9That vasodilator fibers are cholinergic was questioned when it was shown that the dilator neurogenic response in the cat was unaffected by atropine. 10 In this paper, results of a further analysis of the dilator innervation are presented. In addition, the suggestion by Edvinsson and Owman" that the dilator innervation acts by inhibiting sympathetic activity is examined critically. MethodsTissues were removed from exsanguinated cats and rabbits of either sex for in vitro examination. Adult cats (2.2-3.5 kg) were anesthetized with pentobarbital (50 mg/kg, i.p.), and adult white rabbits (2-3 kg) were stunned prior to exsanguination. The entire brain, with ...

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